Project Summary/Abstract Bacterial infection following spinal fusion surgery is a major clinical concern, with 1-10% of patients developing infection despite aggressive peri-operative antibiotic treatments. Upwards of 5 million annual spinal surgeries are predicted by 2030. With only partially effective antibiotic treatments, the cost ($33k-$114k per patient in 2013) and disability burden of infection will continue to rise. More effective means to prevent infection are a cost and clinical imperative. New treatment modalities must eradicate pathogens prior to their adherence to the spinal hardware to be most effective in preventing infection. Based on previous work in our laboratories developing antibacterial implant systems, our hypothesis is that maintaining supra-therapeutic concentrations of prophylactic antibiotics at the hardware site following spinal fusion surgery will lower postoperative infection rates. To test this, we will develop a porous polyether ether ketone (PEEK) vessel coated with polylactic acid (PLA) that clips onto the spinal rod and uses ultrasound (US) to release a combination of prophylactic antibiotics that are loaded within the vessel. Use of a combination of antibiotics is expected to reduce the risk of antibiotic resistant pathogens while also ensuring that all contaminating pathogens, both gram-positive and gram-negative, are eradicated from the surgical site. This system will allow rapid and complete release of antibiotics at supra- therapeutic levels to eradicate contaminating bacteria surrounding the surgical hardware. There are three specific aims: 1: To characterize the release kinetics and stability of the US-triggered prophylactic release system using optimized ultrasound parameters, 2: To assess the ability of the US-triggered system to prevent bacterial colonization of adjacent spinal hardware under in vitro conditions, and 3: To determine the prophylactic utility of the US-triggered system in eradicating bacteria and preventing infection surrounding adjacent spinal hardware in an in vivo model. Throughout this proposed project, the applicant will receive training and support in each area as appropriate to perform the research tasks, gaining invaluable skills and experiences to help advance her career as an independent researcher. The approach detailed in this proposal, as well as the concept and impetus, has arisen through the collaborative efforts of a spinal surgeon, US physicist, basic scientist, biomaterials engineer, and biomedical engineer. It addresses the clinical problem of postoperative spinal infections using innovative applications of proven materials, and can quickly and effectively be translated to the clinical area upon completion of the project. We anticipate that the project will result in an adjunctive therapy capable of lowering infection rates in spinal fusion patients, effectively reducing the pain, disability, and mortality associated with postoperative infection following spinal fusion surgery.